This invention relates to the field of image processing. More particularly, it relates to methods and devices for separating multiply scattered light from directly scattered light. The invention further relates to methods and devices that utilize the resultant data sets in the characterization of an optical target beyond that routinely performed in directly scattered light.
In many imaging applications, the object to be imaged includes a highly remittive layer. When light illuminates such an object, the resulting image consists of a directly scattered light component reflected from this highly remittive layer and a multiply scattered light component that is scattered from points that are within the object but outside the highly remittive layer. Because the layer is highly remittive, the directly scattered light component tends to dominate the image. As a result, it is difficult to capture the multiply scattered light component of the image.
An example of an object having a highly remittive layer is the human retina. In the retina, certain structures are visible only by examination of the directly scattered light component of the image. These structures cannot be seen clearly by examination of the multiply scattered light component. Examples of such structures include small blood vessels and superficial features of the optic nerve head. Conversely, there exist other retinal structures, such as drusen, clumped pigment, choroidal tumors, subretinal new blood vessels, subretinal edema, and the choroidal rim of the optic nerve head, which are visible to a far greater extent in the multiply scattered light component than in the directly scattered light component.
In some applications, such as ophthalmologic ones, it is desirable to locate precisely a structure which can be imaged in the multiply scattered light component with respect to a known feature observable only in the directly scattered light component. For example, it may be useful to know that a particular region of drusen or edema is located near the intersection of two blood vessels. Conversely, it is desirable in some applications to locate precisely a structure that can be imaged in the directly scattered light component with respect to a known feature observable only in the multiply scattered light component. For example, it may be desirable to use the choroidal rim, a feature readily observed in the multiply scattered light component, as a point of reference for imaging blood vessels in the vicinity of the macula.
A known technique for separating a multiply scattered light component from a directly scattered light component is to illuminate the retina with a point light source and to direct the remitted image field through a field stop confocal to the light source. By providing the field stop with a pinhole aperture, one can observe the directly scattered light component of the image. Alternatively, by providing a field stop with an annular opening, one can observe the multiply scattered light component of the image. These techniques are described in Elsner A. E., Burns S. A., Weiter J. J., and Delori F. C., Infrared imaging of subretinal structures in the human ocular fundus, Vision Research 36, 191-205, 1996.
Using the foregoing technique, one can provide a field stop with a pinhole aperture, observe the directly scattered light component of the image, replace the pinhole aperture with an annular aperture, and then observe the multiply scattered light component of the image. By scanning in two dimensions, one can generate a two-dimensional image that includes only the multiply scattered light component and create another image that includes only the directly scattered light component. Similarly, by using known techniques of tomography, one can obtain pairs of cross-sections, each pair including one image based on the multiply scattered light component and another based on the directly scattered light component.
A disadvantage of the foregoing technique is that a significant time interval elapses between the measurement of the directly scattered light component and the subsequent measurement of the multiply scattered light component. This interval arises because of the time required to replace the pinhole aperture with an annular aperture. A lengthy interval leads to artifacts in comparison or other combination of information from the two components. Such artifacts reduce the effectiveness of image or data processing techniques in yielding meaningful information concerning the light scattering properties of the target. A lengthy interval allows potential motion or other alterations concerning the target to preclude accuracy in such observations, comparisons, or computations.
Using the forgoing technique, one can, in principle, precisely locate a structure visible in one component relative to a feature visible in the other component by capturing an image or collecting data restricted primarily to the directly scattered field and overlay it on the image or data of the multiply scattered field. By aligning the image or data from the multiply scattered light component with the image or data from the directly scattered light component, one can endeavor to locate a structure visible only in one component relative to a structure visible only in the other component.
In practice, however, the effectiveness of localization is also severely limited by the time interval that elapses between collecting the data from the directly scattered light component and the multiply scattered light component. This is because a target can undergo motion or change over time. For example, the retina is subject to rapid and unpredictable motion. As a result, in the interval, referred to as a blanking interval, that elapses as the two apertures are alternated, the retina may have moved by some unknown amount or in some unknown direction. Typically the mechanical inertia associated with alternating between two apertures prevents the blanking interval from being made short enough to capture two successive images without significant alteration to the target, e.g. movement of the retina, between images. Since a patient cannot entirely control eye movements, the position of the retina during observation of the multiply scattered light component will, in general, not be the same as the position of the retina during observation of the directly scattered light component. This unpredictable motion or alteration of the target, e.g. the retina, causes unpredictable errors in the reliable alignment of two or more image components or data sets and the further processing of the data therein.
What is desirable in the art is an apparatus and method for reducing the blanking interval, thereby permitting observation of the directly scattered light component and the multiply scattered light component of a target at least substantially simultaneously. For example, if the blanking interval could be made short enough, the retinal target would move or be altered by a negligible amount between the observation of the directly scattered light component and the observation of the multiply scattered light component.
This invention provides apparatus and methods permitting an operator to switch easily between observation of the directly scattered light component and observation of the multiply scattered light component of the image. Near simultaneous collection of the separated components allows their use in further observation, comparison, or computations for characterizing an object, specimen, or structure. In certain embodiments, the invention provides apparatus and methods for observation, evaluation, diagnosis, and therapeutic manipulation of anatomical regions of interest. In certain embodiments, the invention provides apparatus and methods for observation, evaluation, diagnosis, and therapeutic manipulation of the human retina. In the ophthalmologic field, it is desirable to provide an imaging apparatus to allow an operator to use substantially simultaneously both the directly scattered light component and the multiply scattered light component of an image of the human ocular fundus to test adequately for potential pathology.
In certain embodiments, the invention provides apparatus and methods for detecting features in one light component to be used as points of reference for locating distinct features in the other light component. In certain embodiments, the invention provides apparatus and methods for aligning the apparatus according to localization information derived from at least one light component.
It is useful to make computations depending on aspects of both components, using information from each either in succession, simultaneously, or in an iterative manner. Such images, imaging data, computation, or simultaneous or successive comparisons are then readily collected and transmittable in a form so as to be useful in the diagnosis and treatment of eye disease.
In certain applications, such as ophthalmologic ones, it is desirable to locate precisely a structure that can be imaged in the multiply scattered light component with respect to a known feature observable only in the directly scattered light component or vice versa. For example, in the eye it may be useful to know that a particular region of drusen, clumped pigment, choroidal tumors, subretinal new blood vessels, subretinal edema, or the choroidal rim of the optic nerve head, each of which is visible in the multiply scattered light component, is located near the intersection of two blood vessels or superficial cysts that are visible in the directly scattered light component from the more superficial layers of the retina.
This invention provides apparatus and methods that permit immediate generation and observation of an entire image derived primarily from multiply scattered light at least substantially simultaneously with an image derived primarily from directly scattered light. The at least substantially simultaneous generation and observation of images from each type of scattered light, in accordance with the invention, facilitates localization of features primarily visible in one component relative to features visible in the other component by reducing to zero duration or nearly eliminating the blanking interval between observations. The blanking interval is reduced such that the target position and orientation do not change substantially between observations. Therefore, localization data determined from the image generated from one light component may be applied readily to the image generated from the other light component, since structures in the target do not move appreciably during the blanking interval.
The structures more visible in multiply scattered light, such as the choroidal rim of the optic nerve head or subretinal new vessel membranes, may be used to locate a specific portion of the retina for further diagnosis or treatment. Localization can be further improved in some cases by combining the information from directly scattered light and multiply scattered light, but this depends upon reliably accurate registration of the information. The multiply scattered light components as disclosed by Elsner et al. (1996) have been difficult to utilize or interpret.
For the purposes of the present invention, the word xe2x80x9cremitxe2x80x9d refers to any instance of optical radiation resulting from an incident illumination, including by way of example transmission, reflection, scattering, and fluorescence; xe2x80x9cremitterxe2x80x9d refers to any object that radiates incident electromagnetic radiation in any way, including by way of example transmission, reflection, scatter, or fluorescence; and xe2x80x9cremittancexe2x80x9d refers to all manner of optical radiation from a target, including by way of example, electromagnetic radiation that is transmitted, reflected, scattered, or fluoresced.
The invention provides, in part, an imaging device having an illumination system, a separation device, and a detection system. In operation, the illumination system directs light to a target, thereby generating remitted light including one or more multiply scattered light components and a directly scattered light component. The remitted light is received by a separation device, which substantially separates the multiply scattered light from the directly scattered light, preferably without requiring a physical change in the configuration, position, or geometry of the separation device. The multiply scattered light may be further separated according to the degree and direction of the multiple scattering, as described in Elsner et al, 1996. The separation device directs the substantially separated light to a detection system, whereby the multiply scattered light and the directly scattered light can be detected separately and substantially simultaneously. The detection system can then generate two or more images or data sets, one based on the directly scattered light component, and the other based on the one or more multiply scattered light components.
The detection system in certain practices of the invention may generate two or more images or data sets based on the degree of scatter and the direction of remission. This provides the advantage of probing optically observable properties of a target, such as retinal tissue, in a manner not limited to light that is remitted along a narrow path from the strongest or closest remitters. The polarization state of light may be used to separate the directly scattered light components from the multiply scattered light components, in that light that has been remitted multiple times on most targets is randomly polarized, even if it started out uniformly polarized.
The separation of light into directly scattered and multiply scattered components, in accordance with the invention, facilitates the probing, identification, and classification of various target structures, examples of which include structures in a highly scattering medium, structures that do not provide a strong index of refraction change within a limited volume of tissue, structures that have surfaces that are not orthogonal to the optical axis of the instrument, structures having boundaries that are not orthogonal to the optical axis of the instrument, structures that lie beneath highly remittive structures, structures that differ in polarization properties, structures with varying amounts of index of refraction change per unit volume, or structures having index of refraction changes insufficient or over too great a volume to provide a strong source of interference for coherence imaging.
Examples of targets in the ophthalmologic field include:
edema, which can provide a graded index of refraction change and contain a variety of compounds not found in that configuration in the healthy eye;
a choroidal new vessel membrane or pigment epithelial detachment, which can have a dome-shaped configuration;
cysts or multi-component new vessel complexes having adjacent or overlapping membranes with borders that are mainly parallel to the axis of the instrument;
drusen, the deeper portion of choroidal new vessels, or the choroidal rim of the optic nerve head, which all lie beneath the highly remittive retina;
macular edema, which may contain proteins, lipids, or other compounds as well as fluid that thickens and elevates the retina;
the birefringent cornea, or the retinal ganglion cell axons found in highly polarized nerve fiber bundles, which themselves are understood to have a strong axis of polarization;
choroidal melanoma, which is characterized by nonuniform pigment and blood vessel distribution, and which may therefore absorb varying degrees of light compared to adjacent healthy or abnormal ocular issue; and
edematous structures, particularly beneath the retina, which typically do not provide a strong index of refraction change within a small interior volume, particularly when a remittance passes through the scattering overlying structures.
Several classes of embodiments are described. One example includes two remitted light components. These components include, but are not limited to, a directly backscattered light component remitted from an object illuminated on the optical axis of the imaging device and detected on axis and in alignment with an aperture; and a multiply scattered light component that cannot in entirety pass through an aperture that is on the optical axis when the object is illuminated on axis.
A second example provides two or more multiply scattered light components to generate a scattering function. In an embodiment, the edematous structures in and beneath the retina may be probed with such techniques. This example includes, but is not limited to, a first light component that is scattered in a different direction from, or from a smaller focal volume than, the light in a second light component. This permits calculation of a scattering function to characterize the target and structures within it. In an embodiment, such characterization allows the probing of index of refraction changes to detect and quantify properties of structures that do not necessarily have a sharp index of refraction change.
In a third example, the state of polarization of the remitted light is the separation parameter to obtain the directly scattered light component and the multiply scattered light components. One application of such an embodiment is the detection of drusen and other pathological features that remit light in a manner that loses uniform polarization. Light having an initial polarization tends to lose this polarization progressively as it is repeatedly scattered. Light that loses its initial polarization in this way is said to be xe2x80x9crandomly polarizedxe2x80x9d or xe2x80x9cdepolarized.xe2x80x9d For light remitted from drusen and other pathological structures, the loss of polarization occurs because such features lie beneath the retinal nerve fiber layer. Light remitted from these features is scattered and depolarized to a greater extent than is light remitted from the retinal nerve fiber layer, a highly remittive layer that retains polarization to a much greater degree. This example includes, but is not limited to, a first component containing light that retains a greater degree of its initial polarization due to being scattered a relatively fewer number of times prior to reaching the detector, and a second component containing light that retains a lesser degree of polarization due to being scattered a relatively greater number of times. An embodiment according to this example permits a more detailed analysis and improvement of the images or data from the directly scattered light component by quantifying both the polarization state and the position of the remitted light, while the multiply scattered light is derived from those light components that are randomly polarized with respect to the illumination on the target. The remitted light may be analyzed by separating it into two orthogonal polarization states that are detected simultaneously or near simultaneously, or into a series of states that are detected in an exactly or nearly simultaneous manner.
Polarization analysis, termed xe2x80x9cpolarimetry,xe2x80x9d is widely practiced in the art. Most general polarimeters use the Stokes formalism, and can be made to detect scattered light. Multiply scattered or depolarized light is typically discarded as contaminating radiation. However, as disclosed herein, the analysis of images derived from such light, in accord with practice of this invention, is a particularly powerful method for observation.
In one aspect of the invention, an illumination source directs light onto a target point. Light remitted from this illuminated target point includes a directly scattered light component and at least one multiply scattered light component. A field stop separates the remitted light into these two constituent components and directs the two components to one or more detectors. The field stop is adapted to permit detection of the directly scattered light component and the at least one multiply scattered light component without a physical change in the configuration, placement, or geometry of the field stop, e.g., by using reflective, transmissive, or polarization properties, thereby permitting the two components to be detected at least substantially simultaneously. Moreover, this invention can be practices with exactly simultaneous detection.
The source may be, but is not limited to, a laser, a light emitting diode, a single vertical cavity surface emitting laser (VCSEL) element, an array of VCSEL elements, or a well-focused arc lamp, or any source of light that may be focused sufficiently to serve as a point source and be separated by a system of confocal apertures, or be sufficiently uniformly polarized to undergo separation using polarization state analyzers. A source with relatively low absorption in some wavelengths, such as near infrared wavelengths, compared to other wavelengths, allows for multiply scattered light to be detected. In targets such as the human retina, there is relatively low absorption in the near infrared portion of the spectrum compared with visible wavelength light.
In one embodiment of the invention, the field stop for separating the components of the image includes a first region optically conjugate to the illuminated point and a second region adjacent to the first region. The first region of the field stop can be adapted to receive primarily directly scattered light. The second region of the field stop can be adapted to receive primarily multiply scattered light. Similarly, the first region can be adapted to receive light that is scattered a relatively few number of times, or over a relatively narrow focal volume, while the second region can be adapted to receive light that is scattered a relatively greater number of times or over a relatively broader focal volume. Further, the first region can be adapted to receive light remitted primarily from one direction, while the second region can be adapted to receive light remitted primarily from another direction, so that further comparisons may be made to characterize the target according to its scattering characteristics. This differs from the common method of producing stereo image pairs, one difference being that the computations are not limited to computations of relative geometric distances.
In another example, the first region can be adapted to receive light in one polarization state, and the second region can be adapted to receive light in another polarization state for the purpose of exactly or nearly simultaneous collection of light having varying degrees of multiple scatter. As successive, multiple scattering of light decreases the uniformity of the axes of polarization regardless of the axes of initial polarization, separating polarized light from depolarized light results in separation of the directly scattered light from the at least one multiply scattered light component. Separation of multiply scattered light from directly scattered light on the basis of polarization state may employ comparison of the extent of polarization without regard to the axes of polarization. Optical properties of targets may be characterized by polarization axes of remitted light.
In a further practice of the invention, the field stop may include more than two such regions, for the purpose of separating the remitted light into more than two components. This feature can enable analysis of two or more multiply scattered light components distinguished by the angles or distances at which they are remitted from the target or by other criteria apparent to one of skill in the art. Analysis of multiply scattered light components separated according to this feature of the invention facilitates superior characterization of the sample than is possible by consideration of directly scattered light alone, as is commonly practiced in confocal microscopy. In one example, a structure that has a stronger index of refraction change within a given volume of target will produce components that are scattered fewer times than one that has a weaker index of refraction change, for example due to fluid infiltration associated with edema. Other factors being equal, the less edematous tissue will scatter the light over a smaller volume than will the more edematous tissue. In another example, the structures contained within a volume of the target that are large or of uniform construction and oriented in a relatively perpendicular axis to that of illumination will direct their remittance back in the direction of the illumination, or remit it in a forward direction. Such a structure is the nerve fiber layer and the vitreous interface where it is perpendicular to the target. The structures that are small and relatively randomly oriented will scatter little of the light directly back toward the source of illumination and remit in a broad angle. Such structures are the compounds found within the fluid in a pigment epithelial detachment. In a third example, the detection and localization of the structures that cause multiple scattering events may be improved by using two or more multiply scattered light components collected separately so that light tissue interactions that create a shadowing effect that is visualized as the border of a structure may be combined to obtain a larger or better specified border. An example of this is a region of drusen. One benefit is that sources of scatter that lie outside the plane of focus have a potentially more uniform distribution from the different directions sampled than if sampled from only one direction. These sources of scatter may be removed by comparison or subtraction from the multiply scattered light that characterizes the target.
In one practice of the foregoing embodiment, the second region can be a reflective surface and the first region can be a pinhole aperture in the reflective surface. In this embodiment, the directly scattered light can pass through the pinhole aperture and the multiply scattered light component can be reflected by the reflective surface adjacent to the pinhole aperture. A detector in optical communication with the pinhole aperture can detect the directly scattered light component passing through the pinhole aperture. Another detector in optical communication with the reflective surface surrounding the aperture can detect the multiply scattered light component reflected by the reflective surface. Accordingly, the directly scattered light component and the multiply scattered light component can be detected substantially simultaneously by two different detectors.
Similarly, the light passing through a somewhat smaller aperture or one that is somewhat less displaced with respect to the optical axis of illumination can have undergone scattering a relatively fewer number of times, in comparison to light remitted from a relatively smaller focal volume, or remitted light from a predominantly different direction than light passing through a somewhat larger aperture or displaced somewhat more. Accordingly, the two or more components differing in the aforementioned scattering properties can be detected at least substantially simultaneously by two or more different detectors. A scattering function for regions within the target may then be computed from data derived from the two or more components.
Alternately, the first region can be a reflective surface and the second region can be an annular aperture surrounding the reflective surface. Thus, the multiply scattered light can pass through the aperture, and the reflective surface within the annular aperture can reflect the directly scattered light component of the image.
Similarly, the light reflecting from a somewhat smaller area or one that is somewhat less displaced with respect to the optical axis of illumination can have scattered a relatively fewer number of times, in comparison to light remitted from a relatively smaller focal volume, or from a predominantly different direction than light reflecting off a somewhat larger area or displaced somewhat more. Accordingly, the two or more components differing in the aforementioned scattering properties can be detected substantially simultaneously by two or more different detectors.
The separation of directly scattered and multiply scattered light can also be realized by providing a first region that comprises the end of an optical fiber or a portion of an end of an optical fiber bundle having a plurality of fibers. In this realization of the embodiment, the directly scattered light component incident on the end of the optical fiber can be transmitted through the fiber to a detector.
In certain embodiments, the functions of separation and of detection can be consolidated, e.g., by using a bundle of optical fibers. In such embodiments, the first region comprises one or more fibers of the bundle, and the second region comprises other fibers of the bundle. Thus, as described above, fibers of the first region can transmit the directly scattered light component to a first detector, and fibers of the second region can transmit the directly scattered light component to a second detector or detectors, thereby permitting the directly scattered light component and the multiply scattered light components to be detected individually.
A further embodiment of the invention employs time-division multiplexing and a single detector in optical communication with a separation device, which detects both the directly scattered light component and at least one multiply scattered light component of the remitted light. In this embodiment, the illumination source can be capable of alternately emitting light from two or more adjacent locations. The light is emitted toward the target and subsequently remitted toward a separation device. The separation device can have a first region in optical communication with a detector and a second region adjacent to the first region. In operation, light from one location of the illumination source can be directed to a target during a first interval. The target then remits light comprising a directly scattered light component and a multiply scattered light component or components.
The separation device can be configured such that the first region receives primarily directly scattered light when the target is illuminated with light from the first location, and the second region receives primarily the multiply scattered light. Light from the second location of the illumination source can then be directed to the target, whereby the directly scattered light component of the remitted light is directed to the second region of the separation device and the first region receives primarily multiply scattered light, which is directed to the detector. Thus, rapid alternation between light emitted by the at least two locations of the illumination source enables the directly scattered light component and the at least one multiply scattered light component remitted by the target to be detected substantially simultaneously. The rate at which the light switches between illumination source locations is directly related to the rate at which the detection switches between remitted light components.
Similarly, the first light source location can be positioned with respect to the target and first region such that the light reaching the detector during the first interval is scattered a relatively fewer number of times, from a relatively smaller focal volume or from a relatively different direction, than the light reaching the detector during the second interval. Thus, rapid alternation between light emitted from two or more locations of the illumination source permits multiply scattered light components and directly scattered light components remitted by the target to be detected substantially simultaneously. This and other embodiments of the invention can be constructed to enable two or more locations of illumination to be detected during two or more different time intervals. A plurality of locations disposed in a two-dimensional array may be used as an illumination source, as described in Elsner et al, 1998a.
One illustrative embodiment has two light sources, with a first source and a second source adjacent to the first light source, to illuminate adjacent points on the target in alternate intervals. During a first interval, the first source illuminates the target at a first illuminated point optically conjugate to a pinhole aperture in a field stop. Directly scattered light from the first illuminated point can pass through the pinhole in the field stop to the detector, while most of the multiply scattered light remitted by the target is blocked by the field stop.
During a second interval, the converse occurs. The second source illuminates the target at a second illuminated point optically conjugate to a point adjacent to the pinhole aperture. This second illuminated point is not optically conjugate to the pinhole aperture. Consequently, multiply scattered light, which can originate from areas adjacent to or from a volume surrounding the first illuminated point, passes through the pinhole aperture in the field stop to the detector. Meanwhile, the remainder of the field stop blocks the directly scattered light.
In a further embodiment, a single detector can receive the directly scattered light component and the multiply scattered light component of the image during alternate intervals, without the need to move or alter mechanically the field stop between intervals in order to switch between the directly scattered mode and the multiply scattered mode. In such an embodiment, the light component in optical communication with the detector is determined by the illumination source active during a given time interval, rather than by making any physical change to the field stop. For example, illumination from one source location may cause predominantly directly scattered light to impinge on the detector, while another source location may cause predominantly multiply scattered light to impinge on the detector. This switching action can be performed electronically, and thus can be effected much more rapidly than the mechanical switching action associated with altering the geometry of the field stop. In particular, the switching action can occur so rapidly that the retina may move not at all or by only a negligible amount in the blanking interval between the end of the first time interval and the beginning of the second time interval.
In another embodiment, a target having a surface, such as a retina, can be imaged using a scanning technique. For example, light may be directed to a series of two or more points on the target surface, and light remitted by the target points may be separated into directly and multiply scattered light components and individually detected. One image of the target surface can then be generated from the multiply scattered light components, and a second image of the surface can be generated from the directly scattered light components. In such embodiments, the apparatus can include a positioning device for directing light from the light source to a series of two or more selected points on the target surface. In an embodiment, the positioning device moves the light source relative to the subject. This movement includes at least one of moving the light source and moving the subject.
In related embodiments, optical fibers or fiber bundles can be employed to direct light to the target from two or more locations. Two independent light sources can be employed, e.g., one light source for each optical fiber or fiber bundle. Alternatively, one light source can be coupled to two or more independently controllable optical fibers or fiber bundles, whereby the target can be illuminated by each optical fiber or fiber bundle individually. In an embodiment, optical fibers or fiber bundles may simultaneously function as illumination source locations and also as a separation device. In an embodiment, optical fibers or fiber bundles may simultaneously function as illumination source locations, as a separation device, and as a detection system.
An embodiment of the invention provides an endoscope having optical fibers or fiber bundles. The endoscope facilitates characterization of anatomical structures of interest that are internal to a subject such as an organism or other subject having internal structure not readily visualized from outside the confines of the subject. The endoscope may further comprise apparatus for incident light generating, positioning, separating, detecting, and processing as described herein.
The invention further includes an embodiment in which the polarization properties of the remitted light in conjunction with the controlled polarization properties of the illuminating light enable the separation of directly scattered light from multiply scattered light. The polarization of the illuminating light can be controlled by any of several known polarization controllers, such as a rotating polarizer to alter the axes of one or more single illumination sources, a stationary polarization device that alters the polarization state under electronic control, or time-division multiplexing of the illumination source itself. One example of such time-division multiplexing includes the use of multiple sources and a switching circuit, with the illumination directed at the target by a positioning device. Another example is the rapid alteration of the polarization state of a single source such as a Vertical Cavity Surface Emitting Laser or an illumination source with a polarization state generator.
In one instance, the separation of the remitted light may be performed using polarization multiplexing, and the polarization separation device may direct light to two detectors according to the remitted polarization. By controlling the input polarization temporally, the difference in polarization properties between the illuminating light and the remitted light can be calculated. Multiply scattered light has decreased uniformity with respect to polarization, i.e. is depolarized, or has a greater level of random polarization. As a result, it is detected substantially equally in both detectors, independent of the polarization state of the incident light. In contrast, directly scattered light will retain polarization equal or in some other way related to the polarization of the incident light. Therefore, the polarization separation device will communicate the directly scattered light unequally between the two detectors. In this manner, temporal variation of the polarization properties of the illuminating light separation on the basis of polarization properties allows the discrimination of the directly scattered light component from the multiply scattered components.
In a similar embodiment, a polarization state analyzer can be placed in optical alignment before a single detector, and time-division multiplexing can characterize in a near simultaneous manner the polarization properties along specified axes. In general, those skilled in the art will readily generalize these principles of the invention to include multiple sources with different polarization states and/or multiple separation devices and detectors based on the polarization state of the light remitted from the target.
In one practice of the invention, an apparatus as described above can be employed to generate a three-dimensional image or data set of a subject, such as a biological tissue, using the technique of tomography. In this practice, a directly scattered light image and a multiply scattered light image of the subject are obtained for at least two planes of the subject at differing depths by varying the focal plane of the apparatus. The multiply scattered and directly scattered light images can be ordered in series to generate a three-dimensional image or data set from the multiply scattered light images and to generate a three-dimensional image from the directly scattered light images. Thus, in certain embodiments, the apparatus can include a focusing mechanism or control for changing or varying the focal plane of the apparatus.
In general, the data set may contain several components separated based on the light scattering properties of the light remitted from the target, using any of a variety of separation techniques. Further data processing may then be performed on two or more of these components, resulting in a two or three dimensional characterization of the target that includes at least one multiply scattered light component. Therefore, data generated in this way incorporates information from both types of remitted light, rather than only from directly scattered light. This may facilitate observation, comparison, and therapeutic manipulation of subjects. This practice of the invention hence is not limited to the tomographic computations of peak reflectivity derived from only the directly scattered or transmitted light, as described in Dreher et al, 1991.
The localization of target features, in accord with the invention, in either the multiply scattered light component or the directly scattered light component can improve the localization for diagnosis or therapy in a manual or automatic manner. In a two dimensional application in the ophthalmological field, the localization of the central macula or other retinal regions can be difficult due to disease processes that obscure the retinal anatomy. The choroidal rim of the optic nerve head is more readily visualized as a sharp border that is generally round in shape in multiply scattered light than by the features in directly scattered light. The choroidal rim provides an anatomic landmark for the automatic or manual localization of itself or of neighboring structures such as the macula. This landmark is less disturbed by many disease processes, such as age-related macular degeneration, other adult onset or juvenile macular degenerations, presumed ocular histoplasmosis syndrome, retinitis pigmentosa, diabetic retinopathy, ocular hypertension, retinal artery or vein occlusion, or glaucoma, than are the landmarks readily visible in directly scattered light, including retinal blood vessels.
The choroidal rim landmark in multiply scattered light may also be used for rapid positioning, e.g. in examining a large extent of the fundus, such as in the case of screening for choroidal melanoma. The location of the central macula may be found readily, with the practice of this invention, by positioning the illumination source such that the choroidal rim is located at a specified distance and in a specified direction from the target point being examined. As a result, a typical macula may be located in the center of the measurement field or lying below the center. This may be done in an automatic manner. As reported in Chen et al., 1992, for an adult human eye of typical size and shape, the choroidal rim is roughly 3500 microns nasal to the retina and 0 to 1500 microns inferior to it. These typical measurements vary from subject to subject depending upon the size, shape, and refractive power of the eye. In some cases, the retinal vessels or other features that are detected in directly scattered light may add to the accuracy or rapidity of positioning. Additionally, pathological features such as drusen or new blood vessels that are localized in multiply scattered light may be used singly or in combination with other features such as the choroidal rim or retinal landmarks to facilitate diagnosis, treatment, or any other observation, evaluation, or manipulation of the subject, such as guiding the therapeutic beam of a laser.
In the ophthalmological field, pathology may exist in three dimensions, and diagnosis, treatment, and management following treatment can be improved by obtaining the three dimensional characterization of the pathological tissues. Pathological structures, such as the exudative lesions found in age-related macular degeneration, have features that may be readily found using the multiply scattered light component. The pathological retinal elevation that results from fluid accumulation can be quantified, again by practice of this invention, using the directly scattered light component, as in Kunze et al, 1999. Drusen are another pathological structure that are readily located in the transverse directions using multiply scattered light.
Elsner et al, 1998, reported that the axial transfer function of the directly scattered light component was different from the multiply scattered light component, both qualitatively and quantitatively. A combination of the directly scattered light component and multiply scattered light components may further characterize the target for the purposes of diagnosis, treatment, or management following treatment for drusen or exudation.
In the ophthalmological field, the pathology related to age-related macular degeneration is treated with laser photocoagulation or thermal treatment. In one example, new vessels themselves or their associated membrane are photocoagulated. In another example, the entire region of the membrane is treated with thermal therapy, as in transpupilary thermal therapy over a broad region encompassing exudation. A third example is the use of a laser to apply heat treatment for the reduction of drusen, avoiding the fovea and often the drusen themselves. In addition, there is the application of a therapeutic beam with a photoenhancer, as in photodynamic therapy, to treat new vessel membranes. In all these treatments, the pathology may be localized in the multiply scattered light component. Further precision may be obtained by using the directly scattered light component to localize superficial features, which might be smaller and therefore more accurately placed, as well as more familiar from standard clinical methodologies. As many of these treatments are time consuming and may not require expertise in terms of application, as opposed to making the decision for treatment, automatic application of thermal energy may be localized by using the multiply scattered light component.
In such instruments, the data and/or images pertaining to the multiply scattered light component or computations with both the multiply scattered light component may be better utilized by the addition of training or database functions. Such training may include, but is not limited to, describing how to acquire the multiply scattered light component images or data, with or without the near simultaneous comparisons or calculations from the directly scattered light component. Training may also include how to localize the features or choice and to position a diagnostic or therapeutic instrument.
In an embodiment, data and/or images generated by any apparatus, device, or method described herein, or data and/or images generated as a result of practicing any apparatus, device, or method described herein, may be utilized as training materials to teach individuals to operate or to interpret results generated by any apparatus, device, or method described herein.
In an embodiment, the training function includes distance education. The images or data included in the training may be collected at a first location. The training may occur at a second location. The second location may be the same as the first location or may be remote to the first location. In an embodiment, the training images and/or data are generated at a first location, and training occurs at a plurality of training locations. In another practice, the training images and/or data are generated at a plurality of source locations, and training occurs at a plurality of training locations. In a further embodiment, the training images and/or data are generated at a plurality of source locations, and training occurs at a second location.
The transfer of training images or data between the locations may be accomplished by any means of transmittal, including transfer of written or printed documents, transfer of computer storage media, or transmittal of digital information that identifies or defines written or print documents via facsimile. It will be apparent to one of ordinary skill in the art that other communication techniques, systems, and methods are practicable as well, including cable networks, infrared links, short haul modem link or other types of communication link suitable for carrying data between two or more locations, transmittal of electronic data over a network, transmittal of electronic data over a wireless transmittal, or other such means.
In an embodiment, data and/or images generated by any apparatus, device, or method described herein, or data and/or images generated as a result of practicing any apparatus, device, or method described herein may be stored in a database. Examples of data generated include, but are not limited to, normative data, criteria or parameters that indicate abnormal findings, the confidence level by which to judge the abnormality of the findings, change over time, the confidence level by which to judge the amount and direction of change over time, recommended therapeutic treatment, feedback during treatment, success of the treatment, deviation from results expected due to normative data or therapeutic treatment, and quality of the data.
With respect to retinal disease or evaluation, examples include screening for a disease such as age-related macular degeneration, choroidal melanoma, epiretinal membranes, or macular edema; diagnosis for therapeutic treatment; and localization of pathological features before or during treatment.
In an embodiment, training materials may include data and/or images stored in a database. The training may include instruction on the operation of an apparatus or device, or on the performance of a method. In an embodiment, data and/or images from a database may simulate, for training purposes, data gathered from a subject.
The database may include features detected by collection and analysis of multiply scattered light and data generated therefrom. The database may be an integral part of the apparatus or device and corresponding electronic or computer components. The database may be provided in any form during training, collected during training, collected at the location, or transferred from a remote location. These include, and are not limited to, the detection and localization of features afforded by using multiply scattered light. An example pertaining to the retina is the localization of the choroidal rim of the optic nerve head. This function may facilitate the stabilization of an image or the localization of features in or beneath the retina. The success of localization, the position of the features, and relative locations or other features may be stored for future purposes, such as comparison of data collected from other subjects or collected by other means.
In an embodiment, the database is populated with data collected from a processor, generated from a simulation of a target, or derived from an analytical or computational model of a target.
In an embodiment, the database is adapted to distinguish a target or a portion of a target that is abnormal compared to those values stored in the database and considered normal. This consideration may be based upon human judgment, computational evaluation of the data, or by other methods readily apparent to one of skill in the art.